nach oben

Breast Cancer Research and Treatment

Erschienen in:

01.01.2009 | Preclinical Study

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

verfasst von: Rabab A. A. Mohammed, Ian O. Ellis, Somaia Elsheikh, Emma C. Paish, Stewart G. Martin

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2009

Einloggen, um Zugang zu erhalten

Abstract

Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors, relationship with angiogenesis and whether active lymphangiogenesis occurs within the tumour. A series of 177 well-characterized breast cancers, with long term follow up, were stained with D2-40, CD31 and CD34. Distribution of lymphatics and lymph vessel density (LVD) were assessed in three areas, intratumoural, peripheral and peritumoural and correlated with clinicopathological criteria and patient prognosis. Microvessel density (MVD) was assessed and correlated with LVD. Double immunohistochemical staining with D2-40 and MIB-1 was carried out to assess the proliferative status of lymphatics and of the tumour emboli within. Peritumoural lymphatics were detected in all tumours whereas peripheral and intratumoural lymphatics were detected in 86 and 41% of specimens, respectively. Tumours with higher total LVD were significantly associated with the presence of lymph node (LN) metastasis and shorter overall survival (OS). In multivariate analysis, tumour grade, LN status and the presence of lymphovascular invasion, but not LVD, were independent poor prognostic factors. No association was found between LVD and MVD. Proliferating lymphatics were detected in 29% of specimens and were significantly associated with dense inflammatory infiltrate. In conclusion, lymphatics are located primarily in the peritumoural and peripheral areas in breast cancer and seem to play an important role in disease progression by being routes for tumour dissemination. The lack of correlation between lymphangiogenic and angiogenic characteristics suggests two distinct processes and the presence of active lymphangiogenesis, albeit in a small portion of specimens, may have important therapeutic implications.

Hong YK, Shin JW, Detmar M (2004) Development of the lymphatic vascular system: a mystery unravels. Dev Dyn 231(3):462–473PubMedCrossRef

Al-Rawi MA, Mansel RE, Jiang WG (2005) Molecular and cellular mechanisms of lymphangiogenesis. Eur J Surg Oncol 31(2):117–121PubMedCrossRef

Banerji S et al (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 144(4):789–801PubMedCrossRef

Breiteneder-Geleff S et al (1997) Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol 151(4):1141–1152PubMed

Chilosi M, Doglioni C, Dei Tos AP (2005) New diagnostic markers: podoplanin-d2–40. Pathologica 97(3):158–159PubMed

Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25PubMedCrossRef

Hong YK, Detmar M (2003) Prox1, master regulator of the lymphatic vasculature phenotype. Cell Tissue Res 314(1):85–92PubMedCrossRef

Mohammed RAA et al (2007) Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol 31(12):1825–1833PubMedCrossRef

Leu AJ et al (2000) Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res 60(16):4324–4327PubMed

10.

Padera TP et al (2002) Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296(5574):1883–1886PubMedCrossRef

11.

Pathak AP, Bhujwalla ZM, Pepper MS 92004) Visualizing function in the tumor-associated lymphatic system. Lymphat Res Biol 2(4):165–172PubMedCrossRef

12.

Agarwal B et al (2005) Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol 29(11):1449–1455PubMedCrossRef

13.

Vleugel MM et al (2004) Lack of lymphangiogenesis during breast carcinogenesis. J Clin Pathol 57(7):746–751PubMedCrossRef

14.

Williams CS et al (2003) Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer. J Pathol 200(2):195–206PubMedCrossRef

15.

Van der Auwera I et al (2005) Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study. Clin Cancer Res 11(21):7637–7642PubMedCrossRef

16.

Choi WW et al (2005) Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 18(1):143–152PubMedCrossRef

17.

Bono P et al 2004 High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Cancer Res 10(21):7144–7149PubMedCrossRef

18.

Kato T et al (2005) A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity. Br J Cancer 93(10):1168–1174PubMedCrossRef

19.

Nakamura Y et al (2005) Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. Breast Cancer Res Treat 91(2):125–132PubMedCrossRef

20.

Van der Auwera I et al (2004) Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification. Clin Cancer Res 10(23):7965–7971PubMedCrossRef

21.

Koukourakis MI et al (2005) LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer. J Clin Pathol 58(2):202–206PubMedCrossRef

22.

Mohammed RA et al (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96(7):1092–1100PubMedCrossRef

23.

Weidner N et al (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8PubMedCrossRef

24.

Bevilacqua P et al (1995) Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma–results of a multiparametric study. Breast Cancer Res Treat 36(2):205–217PubMedCrossRef

25.

Toi M et al (1993) Tumour angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer 55(3):371–374PubMedCrossRef

26.

Uzzan B et al (2004) Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res 64(9):2941–2955PubMedCrossRef

27.

Madjd Z et al (2005) High expression of Lewis y/b antigens is associated with decreased survival in lymph node negative breast carcinomas. Breast Cancer Res 7(5):R780–R787PubMedCrossRef

28.

Elston CW, Ellis IO et al (1991): Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410PubMedCrossRef

29.

Singletary SE, Connolly JL (2006): Breast cancer staging: working with the sixth edition of the AJCC cancer staging manual. CA Cancer J Clin 56(1):37–47PubMedCrossRef

30.

Galea MH et al (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef

31.

McShane LM et al (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235PubMedCrossRef

32.

Zeng Y et al (2005) Lymphatic vessel density and lymph node metastasis in prostate cancer. Prostate 65(3):222–230PubMedCrossRef

33.

Koskinen WJ et al (2005) Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression. Radiother Oncol 77(2):172–175PubMedCrossRef

34.

Schoppmann SF et al (2001) Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer. Anticancer Res 21(4A):2351–2355PubMed

35.

Beasley NJ et al (2002) Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 62(5):1315–1320PubMed

36.

Soares AB et al (2007) Lymphatic vascular density and lymphangiogenesis during tumor progression of carcinoma ex-pleomorphic adenoma. J Clin Pathol 60(9):995–1000PubMedCrossRef

37.

Rudolph P et al (1999) Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases. Breast Cancer Res Treat 55(1):61–71PubMedCrossRef

38.

Potemski P et al (2006) Ki-67 expression in operable breast cancer: a comparative study of immunostaining and a real-time RT-PCR assay. Pathol Res Pract 202(7):491–495PubMedCrossRef

39.

van der Schaft DW et al (2007) Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site. Cancer Lett 254(1):128–136PubMedCrossRef

40.

Yamauchi C et al (2007) Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance. Hum Pathol 38(2):247–259PubMedCrossRef

41.

Miyata Y et al (2006) Lymphangiogenesis and angiogenesis in bladder cancer: prognostic implications and regulation by vascular endothelial growth factors-A, -C, and -D. Clin Cancer Res 12(3 Pt 1):800–806PubMedCrossRef

42.

Stefansson IM, Salvesen HB, Akslen LA (2006) Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res 66(6):3303–3309PubMedCrossRef

43.

Sipos B et al (2004) Expression of lymphangiogenic factors and evidence of intratumoral lymphangiogenesis in pancreatic endocrine tumors. Am J Pathol 165(4):1187–1197PubMed

44.

Adams RH, Alitalo K et al (2007): Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8(6):464–478PubMedCrossRef

45.

Maruyama K et al (2005) Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 115(9):2363–2372PubMedCrossRef

46.

Kerjaschki D et al (2005) The crucial role of macrophages in lymphangiogenesis. J Clin Invest 115(9):2316–2319PubMedCrossRef

47.

Yano A et al (2006) Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells. Clin Cancer Res 12(20 Pt 1):6012–6017PubMedCrossRef

48.

Schoppmann SF et al (2002) Tumour-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 161(3):947–956PubMed

49.

Weigelt B et al (2005) Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res 65(20):9155–9158PubMedCrossRef

50.

Hansen S et al (2000) The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients. Clin Cancer Res 6(1):139–146PubMed

51.

Fox SB, Harris AL (2004) Histological quantitation of tumour angiogenesis. APMIS 112(7–8):413–430PubMedCrossRef

Titel: Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications
verfasst von: Rabab A. A. Mohammed
Ian O. Ellis
Somaia Elsheikh
Emma C. Paish
Stewart G. Martin
Publikationsdatum: 01.01.2009
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-9936-1

Springer Medizin

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2009

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial

Ten years of HER2-directed therapy: still questions after all these years

Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women

Racial and ethnic differences in mammography use among U.S. women younger than age 40

Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie